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Experimentos in vitro: XylR-His con bromuro de bencilo Con el fin de confirmar los datos in vivo de la interacción que se establece entre el bromuro de

MATERIALES Y MÉTODOS

2. Entrecruzamiento químico.

2.3 Experimentos in vitro: XylR-His con bromuro de bencilo Con el fin de confirmar los datos in vivo de la interacción que se establece entre el bromuro de

Our longitudinal study showed that temporary parental separation in childhood predicted an increased risk of personality disorders requiring hospitalisation in adulthood. Especially among men, increased risks were found particularly for dramatic cluster personality disorders. The risks for any and for dramatic personality disorders were most elevated among children separated in early childhood, before five years of age, while children separated at later ages did not differ in their risks from the non- separated children. These findings closely correspond to those of Crawford and colleagues (2009), who in their longitudinal study found an effect of parental separation particularly before five years of age on borderline personality disorder symptoms, and to those of the longitudinal study that found that parental separation before three years of age prospectively predicted an increased risk of psychopathic personality disorder (Gao et al., 2010). Also corresponding to our findings, in the NFBC, hospitalisation for any and particularly for dramatic personality disorders was predicted by single parenthood at birth (Kantojärvi, Joukamaa et al., 2008; Mäkikyrö, Sauvola et al., 1998), and children separated from one parent due to parental divorce were also at an increased risk of personality disorders.

The increased risk among the separated, particularly those separated before five years of age, was specific to personality disorders and especially to dramatic personality disorders in that it emerged also in comparison to other severe mental disorders, not only when comparing individuals with personality disorders to healthy controls. No previous longitudinal studies have assessed such specificity of effects directly, although one longitudinal study in a small sample reported no difference in the rates of parental separation among individuals with borderline personality disorder and those with other mental disorders (Helgeland & Torgersen, 2004). However, three retrospective studies did find higher rates of parental separation among individuals with personality disorder compared to the rates found among schizophrenia patients (Byrne et al., 1990; Gibbon et al., 2009; Pert et al., 2004), and are in line with our findings, while one study among depressed subjects found no association between borderline personality disorder and parental separation (Weaver & Clum, 1993).

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Together these findings suggest that parental separation particularly in early childhood may predict the risk of personality disorders and especially of dramatic cluster personality disorders. The findings further suggest that parental separation in early childhood may have particularly strong effects on personality disorders also in comparison to other types of psychopathology. This finding is not surprising, considering that parental separation associates with insecure attachment and with interpersonal difficulties in later life (Gao et al., 2010; Woodward, Fergusson, & Belsky, 2000) and both of these features are highly characteristic of patients with personality disorders (Bakermans-Kranenburg & van IJzendoorn, 2009; Hill et al., 2011).

Compared to the previous studies on parental separation and personality disorders, it is, however, of note that the current study had a larger sample size than the majority of them, was a longitudinal study based on objective measures of parental separation and personality psychopathology, and assessed the effects of this early life adversity on personality disorders across adulthood onwards to later life, while many earlier studies have had follow-ups only to young adulthood. Although thus supportive of most previous findings, ours give strong credence to the hypothesis that early life interpersonal adversity in the form of separation from parents in early childhood may play an etiological role in the development of severe personality disorders.

In addition to personality disorders, previous longitudinal studies have shown that the risks of substance use (Mäkikyrö, Sauvola et al., 1998; Veijola et al., 2008) and mood (Mäkikyrö, Sauvola et al., 1998; Pesonen et al., 2007; Veijola et al., 2004) disorders may also be increased among individuals exposed to temporary separation from their parents. The current study replicated these findings in terms of the increased risk found among the separated children for substance use disorders, but for mood disorders, an increased risk was found for the separated children only in the highest socioeconomic classes.

Previous studies in the HBCS have shown that the children separated from their parents also show, in late adulthood, altered vulnerability to stress, as indicated by altered functioning of the HPA axis (Pesonen et al., 2010), higher systolic blood pressure (Alastalo et al., 2012b) and higher levels of subclinical depressive symptoms (Pesonen et al., 2007) than their non-separated counterparts. Across adult life, they show poorer cognitive functioning (Pesonen, Räikkönen, Kajantie, Heinonen,

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Henriksson, et al., 2011), less social mobility to higher socioeconomic classes (Pesonen, Räikkönen, Heinonen, Kajantie, Osmond, et al., 2011), and a heightened risk of CHD (Alastalo et al, 2009; 2012a). The reproductive functioning of the separated children is altered, with women showing earlier age at menarche and having more children by late adulthood, and men having their first children born earlier and having shorter inter-birth intervals for their children (Pesonen et al., 2008). Overall, these findings correspond well to the DOHaD framework (Barker, 2004, 2009) and to the life cycle model of stress (Lupien et al., 2009), since the separated children, as a consequence of their early life stress exposure, show altered central and peripheral vulnerability to stress, and their risk of somatic illnesses and mental disorders in adult life is increased, particularly in terms of disorders and illnesses known to be associated with changes in the functioning of the stress system (R. Reynolds et al., 2010; Stetler & Miller, 2011).

5.3 Modifying Effects of Sex: Different Etiological Precursors